Many cancers are recalcitrant to treatment because they co-opt the host immune system and evade the endogenous anti-tumor immune response. One such mechanism by which cancer cells evade the immune system is by upregulating immune-inhibitory proteins. Thus, agents that block these immune-inhibitory proteins have been explored as potential therapies that re-enable the endogenous anti-tumor immune response. However, these agents when used alone are ineffective in killing poorly immunogenic tumors. Thus, there is a need for compositions and methods to prevent or treat cancer by promoting the endogenous anti-tumor immune response, in particular in poorly immunogenic tumors. This invention addresses this need.